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Microbial remediation of nitroaromatic compounds (NACs) is a promising environmentally friendly and cost-effective approach to the removal of these life-threating agents. Escherichia coli (E. coli) has shown remarkable capability ...
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Microbial remediation of nitroaromatic compounds (NACs) is a promising environmentally friendly and cost-effective approach to the removal of these life-threating agents. Escherichia coli (E. coli) has shown remarkable capability for the biotransformation of 2,4,6-trinitro-toluene (TNT). Efforts to develop E. coli as an efficient TNT degrading biocatalyst will benefit from holistic flux-level description of interactions between multiple TNT transforming pathways operating in the strain. To gain such an insight, we extended the genome-scale constraint-based model of E. coli to account for a curated version of major TNT transformation pathways known or evidently hypothesized to be active in E. coli in present of TNT. Using constraint-based analysis (CBA) methods, we then performed several series of in silico experiments to elucidate the contribution of these pathways individually or in combination to the E. coli TNT transformation capacity. Results of our analyses were validated by replicating several experimentally observed TNT degradation phenotypes in E. coli cultures. We further used the extended model to explore the influence of process parameters, including aeration regime, TNT concentration, cell density, and carbon source on TNT degradation efficiency. We also conducted an in silico metabolic engineering study to design a series of E. coli mutants capable of degrading TNT at higher yield compared with the wild-type strain. Our study, therefore, extends the application of CBA to bioremediation of nitroaromatics and demonstrates the usefulness of this approach to inform bioremediation research.
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Transdermal drug delivery (TDD) is a non-invasive, topical administration method for therapeutic agents. Transdermal delivery also has advantages including providing release for long periods of time, improving patient compliance, ...
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Transdermal drug delivery (TDD) is a non-invasive, topical administration method for therapeutic agents. Transdermal delivery also has advantages including providing release for long periods of time, improving patient compliance, and generally being inexpensive. Despite these advantages, the use of TDD has been limited by innate barrier functions of the skin. Only small (
This paper reviews transdermal drug delivery systems, recent enhancement techniques to optimize drug delivery such as microneedles and especially vesicular systems.? Herein, we focus on the differences in their composition, physico-chemical properties and applications of those drug delivery systems. We hope recent innovations can work as a foundation for further research and development in transdermal drug delivery system.
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Introduction: RNA interference is a sequence-specific gene silencing phenomenon in which small interfering RNAs (siRNAs) can trigger gene transcriptional and post-transcriptional silencing. This phenomenon represents an emerging t...
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Introduction: RNA interference is a sequence-specific gene silencing phenomenon in which small interfering RNAs (siRNAs) can trigger gene transcriptional and post-transcriptional silencing. This phenomenon represents an emerging therapeutic approach for in vivo studies by efficient delivery of specific synthetic siRNAs against diseases. Therefore, simultaneous development of synthetic siRNAs along with novel delivery techniques is considered as novel and interesting therapeutic challenges.
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1,2-Distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Our pre...
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1,2-Distigmasterylhemisuccinoyl-sn-glycero-3-phosphocholine (DSHemsPC) is a new lipid in which two molecules of stigmasterol (an inexpensive plant sterol) are covalently linked via a succinic acid to glycerophosphocholine. Our previous study revealed that liposome (Lip)-intercalated amphotericin B (AMB) prepared from DSHemsPC (DSHemsPC-AMB-Lip) possesses excellent colloidal properties and in vitro antifungal and antileishmanial activities similar to those of the liposomal AMB preparation AmBisome. The aim of this study was to determine the biodistribution and evaluate the antileishmanial effects of DSHemsPC-AMB-Lip in Leishmania major-infected BALB/c mice. The serum profile and tissue concentrations of AMB were similar in DSHemsPC-AMB-Lip- and AmBisome-treated mice after intravenous (i.v.) injection. Multiple i.v. doses of the micellar formulation of AMB (Fungizone; 1 mg/kg of body weight), DSHemsPC-AMB-Lip (5 mg/kg), and AmBisome (5 mg/kg) were used in L. major-infected BALB/c mouse models of early and established lesions. In a model of the early lesions of cutaneous leishmaniasis (CL), the results indicated that the level of footpad inflammation was significantly (P < 0.001) lower in mice treated with DSHemsPC-AMB-Lip and AmBisome than mice treated with empty liposomes or 5% dextrose. The splenic and footpad parasite load was also significantly (P < 0.001) lower in these groups of mice than in control mice that received 5% DW or free liposome. The in vivo activity of DSHemsPC-AMB-Lip was comparable to that of AmBisome, and both provided improved results compared to those achieved with Fungizone at the designated doses. The results suggest that systemic DSHemsPC-AMB-Lip administration may be useful for the treatment of leishmaniasis, and because it costs less to produce DSHemsPC-AMB-Lip than AmBisome, DSHemsPC-AMB-Lip merits further investigation.
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Introduction: Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, som...
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Introduction: Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL -17A) expressing CD4(+)T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung.Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017.Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.
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Intravenous administration of Taxotere((R)) (a commercial form of docetaxel, DTX) leads to many problems such as hypersensitivity, hemolysis, cutaneous allergy, and patient refusal due to its prolonged injection. The oral absorpti...
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Intravenous administration of Taxotere((R)) (a commercial form of docetaxel, DTX) leads to many problems such as hypersensitivity, hemolysis, cutaneous allergy, and patient refusal due to its prolonged injection. The oral absorption of DTX is very low due to its hydrophobic nature. The purpose of this study was to prepare and carry out an in vitro evaluation of DTX-loaded nanomicelles for oral administration in order to increase the oral delivery of DTX. Studied formulations were prepared with the two surfactants Tween 20 and Tween 80 and were characterized for their particle size, zeta potential, stability, encapsulation efficiency, stability studies in gastric fluid and intestinal fluid, toxicity studies in C26 colon carcinoma cell line, and cellular uptake. The prepared nanomicelles with particle size of around 14 nm and encapsulation efficiency of 99% were stable in gastric fluid and intestinal fluid for at least 6 h and IC50 decreased significantly after 72 h exposure compared to that of Taxotere((R)). Nanomicelles increased the water solubility of DTX more than 1500 times (10 mg/mL in nanomicelles compared to 6 mu g/mL in water). Results of this study reveal that the new formulation of DTX could be used for the oral delivery of DTX and merits further investigation.
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Background: The multidrug resistance (MDR) of cancer cells has become a great barrier to the success of chemotherapy. Objective: In this study, quantitative structure activity relationship (QSAR) modeling was applied to 46 1,4-dih...
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Background: The multidrug resistance (MDR) of cancer cells has become a great barrier to the success of chemotherapy. Objective: In this study, quantitative structure activity relationship (QSAR) modeling was applied to 46 1,4-dihydropyridine structures (DHPs), and some selectedcompounds were docked. Methods: QSAR was used to generate models and predict the MDR inhibitory activity for a series of 1,4-dihydropyridines (DHP). The DHPs were built and optimized using the Sybyl program (x1.2 version). Descriptor generation was done by DRAGON package. Docking wascarried out using Auto Dock 4.2 software. Multiple linear regression, and partial least square were performed as QSAR modelgeneration methods. External validation, cross-validation (leave one out) and y-randomization were used as validation methods. Results: The constructed model usingstepwise-MLR and GA-PLS revealed good statistical parameters. In the final step all compounds were divided into two parts: symmetric (PLS) and asymmetric (MLR) 1,4-dihydropyridines and two other models were built. The square correlation coefficient (R2) and root mean square error (RMSE) fortrain set for GA-PLS were (R2 = 0.734, RMSE train = 0.26). Conclusion: The predictive ability of the models was found to be satisfactory and could be employed for designing new 1,4-dihydropyridines as potent MDR inhibitors in cancer treatment. 1,4- Dihydropyridine ring containing protonablenitrogen as scaffold could be proposed. Sulfur, ester, amide, acyle, ether, fragments are connected to a 1,4-dihydropyridine ring. Phenyl groups (with an electronegative substituent) as a lipophilic part are essential for the inhibitory effect.
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Fifteen compounds related to ameltolide with sodium channel inhibitory activity were subjected to a molecular docking study. The chemical structures of all compounds were built using the program Hyper Chem and conformational studi...
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Fifteen compounds related to ameltolide with sodium channel inhibitory activity were subjected to a molecular docking study. The chemical structures of all compounds were built using the program Hyper Chem and conformational studies were performed with a semiempirical method followed by the PM3 method. A docking study was performed using the program Auto Dock on all the compounds. To confirm the binding mode of inhibitors, molecular dynamics simulations were performed using GROMACS 4.5.5, based upon the docked conformation of ameltolide. The docking analyses indicated that these compounds interacted mainly with residues II-S6 and III-S6 of NaV1.2 by making hydrogen bonds and (pi - pi) interactions with domains I, III, and IV in the channel's inner pore. Our docking study reveals that amide linker plays a major role in the drug receptor interaction. The results of molecular dynamic simulations confirmed the binding mode of ligands, the accuracy of docking, and the reliability of active conformations obtained by Auto Dock.
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A nanocomposite was prepared with reduced graphene oxide, gold nanoparticles and an electropolymerized film made from 2-amino-5-mercapto-1,3,4-thiadiazole. An electrochemical sensor for doxorubicin (DOX) was constructed by modifyi...
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A nanocomposite was prepared with reduced graphene oxide, gold nanoparticles and an electropolymerized film made from 2-amino-5-mercapto-1,3,4-thiadiazole. An electrochemical sensor for doxorubicin (DOX) was constructed by modifying a glassy carbon electrode (GCE) with the nanocomposite. The modified GCE was studied by electrochemical techniques which showed it to enable highly sensitive sensing of DOX. Response (typically measured at a typical working potential of -0.56 V vs. Ag/AgCl) is linear in the 30 pM to 30 nM and 30 nM to 30 mu M DOX concentration ranges, with a limit of detection (LOD) of 9 pM (at an S/N ratio of 3). The method was applied to the determination of DOX in serum and gave recoveries that ranged between 92 and 108%.
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Background: P-glycoprotein (P-gp) causes the efflux of cancer chemotherapy drugs from tumor cells, so its inhibition can be one target for designing and synthesis of new anticancer drugs.
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